Authors:Elena Boldyreva, V. Drebushchak, I. Paukov, Yulia Kovalevskaya, and Tatiana Drebushchak
Monoclinic (I) and orthorhombic (II) polymorphs of paracetamol were studied by DSC and adiabatic calorimetry in the temperature
range 5 - 450 K. At all the stages of the study, the samples (single crystals and powders) were characterized using X-ray
diffraction. A single crystal → polycrystal II→ I transformation was observed on heating polymorph II, after which polymorph
I melted at 442 K. The previously reported fact that the two polymorphs melt at different temperatures could not be confirmed.
The temperature of the II→I transformation varied from crystal to crystal. On cooling the crystals of paracetamol II from
ambient temperature to 5 K, a II→ I transformation was also observed, if the 'cooling-heating' cycles were repeated several
times. Inclusions of solvent (water) into the starting crystals were shown to be important for this transformation. The values
of the low-temperature heat-capacity of the I and II polymorphs of paracetamol were compared, and the thermodynamic functions
calculated for the two polymorphs.
Authors:G. Perlovich, Tatyana Volkova, and Annette Bauer-Brandl
The thermodynamic relationship between crystal modifications of paracetamol was studied by alternative methods. Temperature
dependence of saturated vapor pressure for polymorphic modifications of the drug paracetamol (acetaminophen) was mea sured
and thermodynamic functions of the sublimation process calculated. Solution calorimetry was carried out for the two modifications
in the same solvent. Thermodynamic parameters for sublimation for form I (monoclinic) were found: ΔGsub298=60.0 kJ mol−1; ΔHsub298=117.9�0.7 kJ mol−1; ΔSsub298=190�2 J mol−1 K−1. For the orthorhombic modification (form II), the saturated vapor pressure could only be studied at 391 K. Phase transition
enthalpy at 298 K, ΔHtr298(I→II)=2.0�0.4 kJ mol−1, was derived as the difference between the solution enthalpies of the noted polymorphs in the same solution (methanol). Based
on ΔHtr298 (I→II), differences between temperature dependencies of heat capacities of both modifications and the vapor pressure value
of form II at 391 K, the temperature dependence of saturated vapor pressure and thermodynamic sublimation parameters for modification
II were also estimated (ΔGsub298=56.1 kJ mol−1; ΔHsub298=115.9�0.9 kJ mol−1; ΔSsub298=200�3 J mol−1 K−1). The results indicate that the modifications are monotropically related, which is in contrast to findings recently reported
found by classical thermochemical methods.
Authors:Igor E. Paukov, Yulia A. Kovalevskaya, Alexei E. Arzamastcev, Natalia A. Pankrushina, and Elena V. Boldyreva
solutions, neighboring molecules in the crystals or glasses, excipients in the drug-excipient formulations) [ 1 – 7 ]. Thermodynamic properties have been studied in details for the polymorphsofparacetamol [ 8 ], which contains the acetamide group linked to
Authors:Ricardo Picciochi, Hermínio Diogo, and Manuel Minas da Piedade
Combustion calorimetry, Calvet-drop sublimation calorimetry, and the Knudsen effusion method were used to determine the standard
(po = 0.1 MPa) molar enthalpies of formation of monoclinic (form I) and gaseous paracetamol, at T = 298.15 K:
were used to assess the predictions of the B3LYP/cc-pVTZ and CBS-QB3 methods for the enthalpy of a isodesmic and isogyric
reaction involving those species. This test supported the reliability of the theoretical methods, and indicated a good thermodynamic
consistency between the
Authors:Martin Tjahjono, Martin Karl Schreyer, Liangfeng Guo, and Marc Garland
, Kovalevskaya , YA , Drebushchak , TN . 2004 DSC and adiabatic calorimetry study of the polymorphsofparacetamol. An old problem revisited . J Therm Anal Cal. 77 : 607 – 623 . 10.1023/B:JTAN.0000038998.47606.27 .
, TV , Bauer-Brandl , A . Polymorphismofparacetamol: Relative stability of the monoclinic and orthorhombic phase revisited by sublimation and solution calorimetry . J Therm Anal Calorim 2007 89 : 767 – 774 10.1007/s10973